Studies on the mechanism of ligand-induced modulation of the asialoglycoprotein receptor on hepatoblastoma cells, HepG2, have shown the resultant down-regulation to arise from an alteration in the biosynthesis of sialic acid. Examination of the individual enzymatic reactions leading to the formation of sialic acid in vitro revealed no significant difference in the biosynthetic capacity of the control versus the modulated cells. This finding contrasts with the drastic reduction in synthesis exhibited by intact cells and is suggestive of a broader mechanism for the regulation of cell-surface sialic acid. An investigation of CD4, the presumed T-cell receptor for the human immunodeficiency virus, has shown that surface expression of this protein is blocked by tunicamycin, a potent inhibitor of glycosylation, under conditions where alternate surface receptors are unaffected. Initial studies employing acute lymphoblastic leukemic cells have been extended by the successful transfection of a plasmid containing the cDNA for CD4 into Chinese hamster ovary cells. Subsequent cotransfection with another plasmid containing the multiple drug resistant gene, has permitted the isolation of stable clones expressing large amounts of CD4. Preliminary data or this material indicates the presence on CD4 of complex or multi- artennary hybrid oligosaccharides.